Systems for providing electrical stimulation to an identified location in the brain for specific therapies are coming into increased use for various purposes. Specifically, such systems have been used for treating Parkinson's Disease Tremor and Essential Tremor. A typical electrical brain stimulation system comprises a pulse generator operatively connected to the brain by a lead. The lead has one or more stimulating electrodes at its distal end, designed to be implanted within the patient's brain at a precise location, so that the electrode or electrodes are optimally and safely positioned for the desired stimulation. Reference is made to U.S. Pat. No. 5,464,446, "Brain Lead Anchoring System," assigned to Medtronic, Inc., which is incorporated herein by reference, and which illustrates an effective lead anchoring system and discloses a method of positioning the stimulating lead so that the electrodes are at the desired stimulation site. The lead is positioned using a stereotactic instrument, which permits a very precise movement, e.g., .+-.1 mm, within the brain.
This invention addresses the initial step in functional stereotactic surgery, which is the localization or mapping of functional brain structures. It is to be noted that in many cases of Parkinson's Disease and Essential Tremor, the target is relatively easy to find, so that precise localization may not be necessary. However, other brain targets, such as in cases of advanced Parkinson's Disease, require the localization step. Generally, whenever the target is relatively new, in the sense of lacking statistical data which reliably identifies the target location, it is necessary to first determine where, within the boundary of the functional target area, stimulation can be delivered which is effective and which does not cause problems.
Therapeutic benefit and non-desired effects of brain lesioning and chronic neuromodulation depend critically on this localization procedures. This procedure involves three primary steps. First, anatomical localization of brain targets is determined using anatomical brain atlases, imaging by means of positive contrast x-rays, CT or MRI under stereotactic conditions. Thus, standard imaging techniques are used to make a first determination of coordinates for the lead's target. Next, electrophysiological identification of functional boundaries between brain structures is carried out by means of single cell recording of characteristic cell discharge patterns. This procedure requires use of an electrode which is small enough to differentiate single cells, and thus requires a micro-electrode with a very small surface area, e.g., less than one square micro-meter. The third step involves electrical test stimulation within determined functional brain structures, for the final evaluation of the efficacy of the location. Test stimulations are necessary to determine (1) efficacy of stimulation in the identified functional brain structure; and (2) any side effects caused by stimulation of the brain in this area. If the stimulation electrode is too close to the boundary of the functional brain structure, the function of adjacent brain structures will be modulated, which may lead to undesired side effects. The test stimulations are clinically most relevant when done with an electrode or electrodes with a similar surface area to that of the chronic implantable electrodes, e.g., in the range of about 1-20 square milli-meters.
As currently performed, the second and third steps, namely identification of functional boundaries with a micro-electrode and test stimulation with a larger, or macro-stimulation electrode, require first placement of the micro-electrode, withdrawal of same and then placement of the macro-electrode. These replacements require extra penetrations of the brain tissue, and therefore increase the risk of intra-cranial hemorrhages with severe permanent disability as a potential consequence. It has not been possible to perform effective test stimulation with the micro single cell electrode, because the volume of brain tissue that can be stimulated with the micro electrode is in general insufficient to evaluate efficacy and side effects. For example, our evaluation of functional stereotactic implantation of the Sub-Thalamic Nucleus (STN) or the Globus Pallitus Internae (GPi) reveals a discrepancy between electrical test stimulation with the micro single cell recording electrode and electrical stimulation with a chronic stimulation electrode. This discrepancy is most likely due to the very large difference of the electrode surface area, i.e., less than 1 square micro-meter vs. 1-20 square milli-meters, and the directly associated current density which results in stimulation of largely different volumes of cells, and therefore results in different therapeutic effects and side effects.